Flamazine C (Silver Sulfadiazine – Chlorhexidine Digluconate)

FLAMAZINE® C

Smith & Nephew

Silver Sulfadiazine – Chlorhexidine Digluconate

Topical Antibacterial

Action And Clinical Pharmacology: The mechanism of silver sulfadiazine’s antibacterial action has not been fully elucidated. After exposure to the drug, structural changes in the bacterial cell membrane occur, including distortion and enlargement of the cell and a weakening of the cell wall membrane. This is accompanied by reduced viability in sensitive strains.

The silver sulfadiazine molecule dissociates and the silver moiety is bound to the bacterial cells. It is believed that, after penetrating the cell wall, the silver moiety is attached to deoxyribonucleic acid (DNA) and prevents bacterial cell proliferation. There is approximately 100 times more DNA in mammalian cells than in bacterial cells. It is thought that the ratio of silver sulfadiazine to bacterial DNA is sufficiently high to prevent bacterial division but the corresponding ratio to epithelial DNA is low enough not to block epithelial cell regeneration.

The sulfadiazine moiety also provides a bacteriostatic action against sensitive organisms.

It has been suggested that the presence of chlorhexidine in subminimal inhibitory concentrations does not alter the cell membrane sufficiently to permit the efflux of nitrogen bases, nucleotides and nucleosides, but the alteration is sufficient to permit the entry of sulfadiazine molecules. The combination of these drugs may be bactericidal.

In adults, up to 10% of the sulfadiazine may be absorbed and 60 to 85% of the absorbed amount is excreted in the urine. In children with 13% body surface area burns, the urinary sulfadiazine concentration was 31.8 mg/L.

Percutaneous absorption studies in rats and man with radio-labelled chlorhexidine, have shown that less than 1% of the applied quantity was absorbed across the skin. Oral and i.v. studies indicate that over 90% of the drug is excreted in the feces.

Indications And Clinical Uses: For the treatment of leg ulcers, burns, skin grafts, incisions and other clean lesions, abrasions, minor cuts and wounds.

Contra-Indications: Pregnancy and Children: Sulfonamide therapy is known to increase the possibility of kernicterus. Flamazine C should not be used in pregnant females at term, in premature infants, or in newborn infants during the first month of life.

Flamazine C should not be used in patients with a known sensitivity to any of its components.

Manufacturers’ Warnings In Clinical States: Sensitization to topically applied silver sulfadiazine is rarely predicted or proven by patch testing. Caution should be exercised in the use of Flamazine C in individuals who have previously shown sensitization reactions to sulfonamides.

Silver sulfadiazine cream should be used with caution on patients with a history of G-6-PD deficiency as hemolysis may occur.

When treatment with silver sulfadiazine cream involves prolonged administration and/or large burned surfaces, considerable amounts of silver sulfadiazine are absorbed. Serum concentration of silver sulfadiazine may approach adult therapeutic levels (8 to 12 mg%).

Precautions: Flamazine C should be used with caution in patients with significant hepatic or renal impairment.

Leukopenia has been reported following the use of silver sulfadiazine, especially in patients with large area burns. This may be a drug-related effect, and often occurs 2 to 3 days after treatment has commenced. It is usually self-limiting and therapy with Flamazine C does not normally need to be discontinued, as the WBC count usually returns to the normal range in a few days. WBC counts should be closely monitored.

Pregnancy: The safe use of Flamazine C has not been established in pregnancy. Flamazine C should only be used in badly burned pregnant women if the benefit to the patient outweighs the risk to the fetus. Flamazine C should not be used when the patient is near term (see Contraindications).

Drug Interactions: Anionic surfactants: Due to the cationic properties of chlorhexidine, Flamazine C should not be used in conjunction with anionic surfactants.

Enzymatic debriding agents: Flamazine C may inactivate enzymatic debriding agents, thus the concomitant use of these compounds may be inappropriate.

Oral hypoglycemic agents and Phenytoin: In patients with large area burns where serum sulfadiazine levels may approach therapeutic levels, the action of oral hypoglycemic agents and phenytoin may be potentiated and it is recommended that blood levels be monitored.

Cimetidine: In patients with large area burns, it has been reported that co-administration of cimetidine may increase the incidence of leukopenia.

Adverse Reactions: In patients with large area burns, silver sulfadiazine treatment has been reported to have caused a rash in 2 to 5% of patients. Moderate, and usually transient leukopenia has been reported in up to 3 to 5% of patients and occurs within 48 to 72 hours after therapy has commenced, and generally occurs in patients with at least 30% burns. It is usually self-limiting and the leukocyte count is normalized within 2 to 3 days regardless of whether treatment with Flamazine C is continued or terminated.

A very low incidence of photosensitivity, hypersensitivity, and contact eczema reactions have been observed with the use of chlorhexidine preparations.

Caution should be exercised in individuals who have previously shown a sensitization to sulfonamides, however sensitization to topically applied silver sulfadiazine is rarely predicated or proven by patch testing.

Sulfonamide: During the treatment of burns over large body surfaces (greater than 20% body surface area), significant amounts of silver sulfadiazine are systemically absorbed. Therefore, it is possible that any adverse reactions associated with sulfonamides may occur.

Symptoms And Treatment Of Overdose: Symptoms and Treatment: In extensively burned patients or in patients suspected of showing symptoms of excessive absorption, it is important to optimally maintain fluid balance not only to prevent dehydration but also to avoid the possibility of renal impairment.

Dosage And Administration: Burns: The burn wounds should be cleaned and Flamazine C applied over all the affected areas to a depth of 3 to 5 mm.

One technique is to apply the cream with a sterile gloved hand and/or sterile non metallic spatula. Where necessary, the cream should be re-applied to any area from which it has been removed by patient activity.

Flamazine C should be re-applied at least every 24 hours. The wounds may be dressed or left open.

Duration of administration can be from a few days to several months, depending upon the nature and severity of the wound. Treatment should be continued until satisfactory healing has occurred or until the burn site is ready for grafting. The drug should not be withdrawn from the therapeutic regimen while there remains the possibility of infection except if a significant adverse reaction occurs.

A container of Flamazine C should be reserved for use for a specific patient and should be discarded when no longer required.

Availability And Storage: Each g of white cream contains: silver sulfadiazine 1% w/w and chlorhexidine digluconate 0.2% w/w in a water soluble base. Sterile jars of 500 g and sterile tubes of 50 g. Store at 15 to 20°C and protect from light. Discard cream which has darkened.

FLAMAZINE® C Smith & Nephew Silver Sulfadiazine – Chlorhexidine Digluconate Topical Antibacterial

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